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A Novel Candidate Tumor Suppressor, ING1, Is Involved in the Regulation of Apoptosis¹

Department of Medical Biochemistry and Southern Alberta Cancer Research Centre, The University of Calgary, Calgary, Alberta, T2N 4N1 Canada

We have recently cloned a novel growth inhibitor and candidate tumor suppressor called p33^ING1 (I. Garkavtsev et al., Nature Genet., 14: 415–420, 1996). Because some tumor suppressors participate in the regulation of apoptosis, we hypothesized that the ING1 gene may also play a role in this process. Our results show that p33^ING1 levels increase upon the induction of apoptosis in P19 teratocarcinoma cells by serum deprivation. Elevated expression of ING1 in P19 and rodent fibroblast cells containing a tetracycline-controlled human c-myc gene enhanced the extent of serum starvation-induced apoptosis. This suggests that the pathway by which ING1 modulates cell death is synergistic with Myc-dependent apoptosis. Conversely, constitutive expression of an antisense construct of ING1 conferred protection against apoptosis in these cells. These data support the idea that loss of proper ING1 function may facilitate tumorigenesis, in part, by reducing the cell's sensitivity to apoptosis.

¹ Supported by postdoctoral fellowships from the Leukemia Research Foundation (Canada) and Alberta Cancer Board to C. C. H., grants from the Alberta Cancer Board, Cancer Research Society, and Leukemia Research Foundation (Canada) to R. N. J., and grants from the National Cancer Institute (Canada), Canadian Breast Cancer Foundation (Honda Run for the Cure), and Medical Research Council (Canada) to K. R.

² To whom requests for reprints should be addressed. Phone: (403) 220-8692; Fax: (403) 283-8727; E-mail: mjohnst@acs.ucalgary.ca.

Received 12/20/96. Accepted 2/14/97.

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